Conventional chemotherapeutic agents commonly used in treatments against some cancers include alkylating agents such as nitrogen mustards and ethyleneimines; metabolic antagonists such as folic acid antagonist, purine antagonist and pyrimidine antagonist; antibiotics such as actinomycin C and mitomycin C; pituitary adrenal hormone; and alkaloids. These compounds inhibit the growth of some cancer cells by interfering with any of the biological phenomena from DNA to protein synthesis and have direct killing effect on the cells. But the killing effect of these compounds is not selective and affects not only the cancer cells but also normal cells. Therefore, the toxicity of these compounds is unjustifiably greater than their expected effect.
As a result of studies for a compound that has selective effect against transplanted cancer cells, the present inventors have found unexpectedly that anthranyl derivatives of the formula (I) act only on transplanted cancer cells to inhibit their growth or eliminate them. The present invention has been accomplished on the basis of this fact. The mechanism of the peculiar effect of the anthranyl derivatives of (I) is not altogether clear, but presumably they redifferentiate the abnormal cells which are the product of abnormal differentiation of normal cells.
The anthranyl derivatives that can be used in the present invention have the following formula and are listed in Table 1. It is to be understood that the compounds that can be used in the present invention are by no means limited to these derivatives.
TABLE 1 ______________________________________ ##STR3## Compound No. R.sub.1 R.sub.2 Melting point (.degree.C.) ______________________________________ 1 5-Cl H 114-115 2 5-Br H 117-118 3 6-NO.sub.2 4'-CH.sub.3 210-211 4 H 4'-Cl 156-157 5 5-Cl 4'-Cl 214-215 6 5-Br 4'-Cl 213-214 7 5-Cl 4'-OH 240-241 8 5-Cl 4'-OCH.sub.3 144-145 9 5-Br 4'-OCH.sub.3 134-135 ______________________________________
The above named compounds are known: compounds 1, 2, 6 and 9 are described in J.O.C., 25, 1884 (1960), compound 3 in Bull. Soc. Chim. France, 693 (1960), compound 4 in supra (5) 3, 2383 (1936), compound 5 in supra (5) 4, 245 (1937), compound 8 in supra (3) 31, 530 (1904), and compound 7 in J.C.S. 353 (1942). But none of these references teach or suggest the use of the respective compounds for therapeutic purposes.
The treating agents of the present invention can be administered either orally or parenterally in the form of an intramuscular injection, subcutaneous injection, intravenous injection or suppository. The agents can be formulated in a desired preparation such as a tablet, slow release agent, powder, capsule, suspension, injection or supporsitory by a conventional technique. For instance, they can be formulated in a tablet, granule or powder by mixing with a pharmaceutical carrier (e.g. excipient, binder or solvent) such as lactose, starch, mannitol, saccharose, kaolin, crystalline cellulose, talc, calcium, carbonate, magnesium stearate, calcium stearate or hydrogenpotassium phosphate; or they may be formulated in a capsule by filling a hard capsule with granules or powder or filling a soft capsule with a solution in oil; or they may be formulated in a suspension by suspending gum arabic powder or saccharose in an aqueous solution of them and controlling the pH of the suspension; or they may be formulated in an injection by mixing with mannitol. The effective ingredient of the present invention is used in an amount of 10-70 wt% on the basis of the specific form of preparation in which it is administered. The dose varies with the type of abnormal cell to be treated, its severity, and the method of administration, and is usually from 10 mg to 3 g per day.